基于大数据及“有故无殒”理论的常用抗风湿中药肾毒性研究

In recent years, the reports of nephrotoxicity of Chinese herb Medicine has increased a lot, which has a great impact on its clinical usage. However, the reports of the nephrotoxicity of these herb medicine (Chinese Herbs Nephropathy) are mainly based on the animal experiments and individual clinical cases (almost 100% renal damage). In the long-term use of Chinese herb Medicine guided by. differentiation of TCM, the incidence of renal damage of these Chinese的herbs is not as high as the reported. On this account, our study aims to observe that in the guidance of TCM theory, whether these Chinses herb medicine which are reported to be nephrotoxicial has exactly nephrotoxicity in the real ues of clinical environment. If it is really nephrotoxicial, what degree of its toxicity? Is the toxicity related to gender, age, renal function state, primary disease, dosage and frequency? On this basis, according to the theory of “YOU-GU-WU-YUN” from“Huangdi Neijing”, our study will use the animal experiment to explore the reason why the renal damage caused by Chinese herb medicine is mainly reported in animal experiments and in the real clinical environment, guided by TCM theory, the incidence of renal toxicity caused by Chinese herb medicine is considerably lower than which is reported in literatures. The study also aims to clarify the close relationship between the herbal nature (toxicity) with Disease and Syndrome. It will make a beneficial trial for safety assessment of toxic herbs which should be guided by TCM theory.

近年来中草药引发肾损害的报道日益增多，已影响到相关药物的临床使用。但这些中药具有“肾毒性”（中草药肾病）的报道主要见于动物实验研究（肾损害发生率几乎是100%）及临床个案报道，而在长期中医临床辨证论治使用中，中药肾毒性并非如有些报道的那么高。有鉴于此，本课题拟通过大数据研究阐明上述有“肾毒性”的中药在中医理论指导下，在真实使用环境中这些药物是否有“肾毒性”？若有毒性，其毒性程度如何？肾毒性与性别、年龄、患者肾功能的状态、原发疾病、药物的用量、频次等是否有关？在此基础上根据《内经》“有故无殒”理论，通过动物实验进一步探析中草药引发肾损害的报道多见于动物实验研究，而在中医理论指导下，在真实使用环境中，中药肾损害的发生率远低于文献报道那么高的原因，阐明中药药性（毒性）和“病证”之间的密切关系（“有病则病当之，反之无病则体受之”）。也为“有毒”中药须在中医理论指导下进行安全性评价作出有益的尝试。

近年来中草药引发肾损害的报道日益增多，已影响到相关药物的临床使用。但纵观上述中草药具有“肾毒性”的报道，主要见于动物实验研究以及临床个案报道。本次课题通过大数据技术采集近2046万条临床数据信息，发现细辛这类被认为具有肾毒性的常用抗风湿中草药，在实际使用过程中其肾损害发生率均小于2%，显著低于以往的动物实验研究报道，且肾损害以单纯胱抑素C升高为主，并与高龄、大剂量、无配伍使用密切相关，提示临床上在坚持中医辨证论治的原则下，运用君臣佐使的理论配伍使用细辛这类被认为有肾毒性的中草药是相对安全的。同时为进一步探明病/证-毒-效的相关性，本次课题还在“有故无殒”理论指导下，以风寒湿证大鼠和狼疮鼠为研究对象，观察中药细辛在生理状态和病理状态下肾脏毒性的差异。研究发现细辛用于风寒湿证大鼠及狼疮鼠在恰当剂量时主要体现的是治疗作用，而非肾毒性，超过恰当剂量则对肾脏有损害作用。细辛对于病理状态有比正常生理状态下较低的毒性，在一定剂量范围内表现为“有故无殒”，而在此理论指导下正确的辨证论治运用中药则是安全用药的前提。毒性是中药药性的重要组成部，中药毒性的研究不能脱离病证去孤立研究，而应充分考虑药（毒）和病证之间的关系，因此本次课题也为探索一种更符合中医理论及临床实际的中草药毒性研究方法，作出了一次有益的尝试。